Tissue-specific antigen presentation to CD4 T cells during persistent Salmonella Typhimurium infection (P3300)

Abstract

Abstract Antigen presentation is essential for the initiation of a CD4 T cell immune response and is commonly associated with dendritic cells (DCs) presenting foreign antigen to CD4 T cells in the context of MHCII in lymphoid tissue. It is currently unclear as to which antigen presenting cells (APCs) are displaying antigen, and what the impact this has on CD4 T cells throughout a persistent bacterial infection. In this study, we use a murine model of typhoid fever by orally infecting resistant mice with a virulent strain of Salmonella typhimurium tagged with an immunogenic epitope called Eα52-68 peptide (pEα). This allows for the visualization of antigen presentation directly ex vivo at various times after infection through the use of the Y-Ae antibody that specifically recognizes the pEα:MHCII complex. We show that while DCs are the most prominent APC in the infected spleen and mesenteric lymph nodes early, macrophages seem to predominate in the liver. Surprisingly, we could still detect antigen presentation in the spleens of mice infected with pEα-tagged S. typhimurium as late as 120 days post infection. Additionally, interferon-γ responses from effector T cells could be detected directly ex vivo at this late time. These results demonstrate that that cells presenting antigen may differ greatly between persistently infected organs and paves the way to understanding what role this might have in regulating CD4 T cell responses during this type of infection.